Circulation Research. 2003;93:700-709
doi: 10.1161/01.RES.0000094745.28948.4D
doi: 10.1161/01.RES.0000094745.28948.4D
© 2003 American Heart Association, Inc.
Review |
Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A
From the Institute of Pharmacology and Toxicology, Universitätsklinikum Münster, Münster, Germany.
Correspondence to Dr Michaela Kuhn, Institute of Pharmacology and Toxicology, Universitätsklinikum Münster, Domagkstrasse 12, D-48149 Münster, Germany. E-mail mkuhn{at}uni-muenster.de
Rudi Busse Editor
This Review is part of a thematic series on Cyclic GMP–Generating Enzymes and Cyclic GMP–Dependent Signaling, which includes the following articles:
Regulation of Nitric Oxide–Sensitive Guanylyl Cyclase
Cyclic GMP Phosphodiesterases and Regulation of Smooth Muscle Function
Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A
Cyclic GMP–Dependent Protein Kinases and the Cardiovascular System: Insights From Genetically Modified Mice
Regulation of Gene Expression by Cyclic GMP
Explaining the Phenomenon of Nitrate Tolerance
Besides soluble guanylyl cyclase (GC), the receptor for NO, there are at least seven plasma membrane enzymes that synthesize the second-messenger cGMP. All membrane GCs (GC-A through GC-G) share a basic topology, which consists of an extracellular ligand binding domain, a short transmembrane region, and an intracellular domain that contains the catalytic (GC) region. Although the presence of the extracellular domain suggests that all these enzymes function as receptors, specific ligands have been identified for only three of them (GC-A through GC-C). GC-A mediates the endocrine effects of atrial and B-type natriuretic peptides regulating arterial blood pressure and volume homeostasis and also local antihypertrophic actions in the heart. GC-B is a specific receptor for C-type natriuretic peptide, having more of a paracrine function in vascular regeneration and endochondral ossification. GC-C mediates the effects of guanylin and uroguanylin on intestinal electrolyte and water transport and on epithelial cell growth and differentiation. GC-E and GC-F are colocalized within the same photoreceptor cells of the retina and have an important role in phototransduction. Finally, the functions of GC-D (located in the olfactory neuroepithelium) and GC-G (expressed in highest amounts in lung, intestine, and skeletal muscle) are completely unknown. This review discusses the structure and functions of membrane GCs, with special emphasis on the physiological endocrine and cardiac functions of GC-A, the regulation of hormone-dependent GC-A activity, and the relevance of alterations of the atrial natriuretic peptide/GC-A system to cardiovascular diseases.
Key Words: guanylyl cyclase receptors
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